Oral versus intravenous antibiotic therapy for Staphylococcus aureus bacteremia or endocarditis: a systematic review and meta-analysis of randomized controlled trials

Background We conducted a systematic review of randomized controlled trials (RCTs) to generate more precise estimates of the efficacy and safety of oral versus intravenous antibiotic therapy for S. aureus bacteremia or endocarditis. Methods MEDLINE, EMBASE, the Cochrane Library, and Web of Science database were searched through February 21st, 2024. RCTs were included if they compared oral versus intravenous antibiotic therapy for S. aureus bacteremia or endocarditis, and appropriately reported outcomes for each group. Risk of bias was assessed using the revised Cochrane tool for assessing risk of bias in randomized trials. Heterogeneity between studies was evaluated with the Cochran’s Q-statistic and I2 test. Treatment effects were summarized with pooled risk ratios using a random effects model meta-analysis. (PROSPERO CRD42024481512) Results Only four RCTs met criteria for inclusion in meta-analysis. Among participants assessed for treatment failure, there was no difference between the oral and intravenous therapy groups (RR 0.99; 95% CI, 0.63–1.57; I2 = 0%). There was also no significant difference in adverse events between oral and intravenous therapy groups (RR 0.65; 95% CI, 0.07–5.94; I2 = 74%); however, the confidence interval is wide, and heterogeneity was high. Conclusions In this systematic review of RCTs comparing oral to intravenous antibiotic therapy for S. aureus bacteremia or endocarditis, few studies met eligibility criteria for inclusion. Meta-analysis of these studies suggests that transitioning from intravenous to oral therapy is likely effective in a subgroup of carefully selected patients. Additional randomized trials are necessary before transition to oral therapy can be routinely recommended.